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Regeneration and experimental orthotopic transplantation of a bioengineered kidney

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Abstract

Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.

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Figure 1: Perfusion decellularization of whole rat kidneys.
Figure 2: Perfusion decellularization of porcine and human kidneys.
Figure 3: Cell seeding and whole-organ culture of decellularized rat kidneys.
Figure 4: In vitro function of bioengineered kidney grafts and orthotopic transplantation.

Change history

  • 18 October 2013

     In the version of this article initially published, the human kidneys in Figure 2a,b were incorrectly described as porcine and the porcine kidneys in Figure 2c,d were incorrectly described as human in the figure legend. The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

The present study was supported by the US National Institutes of Health (NIH) Director's New Innovator Award DP2 OD008749-01 and departmental funds. J.J.S. was supported by an AΩA Research Fellowship and an American Heart Association Predoctoral Fellowship. The Program in Membrane Biology Microscopy Core is supported by NIH grants DK43351 and DK57521. We further thank Q.C. Ott for critical review and editing of the manuscript. We thank C. Hoffman, J. Beagle and M. Duggan for technical support with urine sample analysis. We thank M. McKee for her expert support with transmission electron microscopy and A. Tisdale for her expert support with scanning electron microscopy.

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H.C.O. conceived, designed and oversaw all of the studies, collection of results, interpretation of the data and writing of the manuscript and was also responsible for the primary undertaking, completion and supervision of all experiments. J.J.S. and J.P.G. performed animal surgeries, conducted decellularization and whole-organ culture experiments and performed in vitro and in vivo testing. S.E.G. was responsible for cell culture, preparation of cell suspensions and matrix characterization. G.G. characterized fetal lung cells and scaffolds and regenerated constructs using various imaging techniques. J.P.V. provided input on tissue engineering aspects and reviewed the manuscript.

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Correspondence to Harald C Ott.

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Song, J., Guyette, J., Gilpin, S. et al. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med 19, 646–651 (2013). https://doi.org/10.1038/nm.3154

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